Interleukin (IL)-21 is an important regulatory cytokine with impact on both innate and adaptive immune cells. It is mainly produced by activated CD4+ T cells, follicular T-helper cells (Th) and natural killer T cells (Leonard et al., 2008) and targets a number of IL-21 receptor-expressing cells, primarily B, T and NK cells but also macrophages and dendritic cells (Spolski and Leonard, 2008). The IL-21 receptor is comprised of an IL-21-specific receptor chain (IL-21Rα) and the common gamma chain (CD132) that is shared by the receptors for IL-2, IL-4, IL-7, IL-9 and IL-15 (Spolski and Leonard, 2008). Important biological effects of IL-21 include the induction of T-cell differentiation into Th17 cells that produce IL-17A and also contributes to IL-21 production (Korn et al., 2007), enhanced proliferation and cytotoxic activity of CD8+ T cells (Liu et al., 2007), functional maturation of NK cells (Brady et al., 2010) and activation of monocytes (Vallières and Girard, 2013). In concert with other cytokines and signaling molecules, IL-21 also regulates the development and activation of B cells into Ig-secreting cells (Ozaki et al., 2004; Moens and Tangye, 2014).
Due to its importance as a regulatory cytokine, an aberrant production of IL-21 may also have pathogenic consequences, and studies in mice have demonstrated its potential involvement in a variety of immune-related conditions including inflammatory disease and autoimmunity (Ozaki et al., 2004; Vinuesa et al., 2005; Vogelzang et al., 2014). In humans, T cells producing IL-21 have been shown to be increased in patients with systemic lupus erythematosus, coinciding with a similar increase in IL-17A producing T cells (Dolff et al., 2011), in rheumatoid arthritis (Ma et al., 2012) and in celiac disease (van Leeuwen et al., 2013). Furthermore, there is evidence for IL-21 serving as a potential tumorigenic factor in certain lymphomas (Lamprecht et al., 2008; van der Fits et al., 2012) but, IL-21 also has the capacity to induce apoptosis in other lymphomas (Akamatsu et al., 2007; Gelebart et al., 2009).
Granted patents relating to medical uses of known antibodies (such as anti-CD22) directed to an epitope on a molecule are known in the art. An example is EP0969866 B2 wherein neither the amino acid sequence of the anti-CD22 antibody, nor the sequence of residues on CD-22 molecule, are disclosed. However, to our knowledge, prior art documents are silent about medical uses (as well as compositions, kits and methods of treatments thereof) antibodies with different specificities for the treatment IL-21.
Consequently, there is a need to inhibit and/or neutralize IL-21 mediated activation of human cells for the prophylaxis and/or treatment of the above mentioned diseases and conditions.